Interaction between histamine and adenosine in human cerebromicrovascular endothelial cells: modulation of second messengers.

This study demonstrates the presence of histamine H1 and H2 receptors and purinoreceptors A1 and A2 on endothelial cells derived from human brain microvessels (HBEC). Histamine induced formation of both inositol triphosphate (IP3) (EC50 = 10.2 +/- 0.9 microM) and cyclic adenosine monophosphate (cAMP) (EC50 = 5.2 +/- 0.9 microM) in HBEC in a concentration-dependent fashion. IP3 formation was inhibited by H1 receptor antagonists mepyramine maleate and chlorphenyramine, but not by H2 receptor antagonist cimetidine. Production of cAMP was efficiently inhibited by cimetidine. Selective A1 receptor agonists decreased, whereas A2 receptor agonists increased cAMP production in HBEC. When added together with histamine to HBEC cultures, both A1 and A2 receptor agonists diminished histamine-induced IP3 stimulation. This effect was reversed in the presence of specific A1 and A2 receptor antagonists, respectively. Marked augmentation of histamine-induced cAMP production by HBEC was observed in the presence of A2 agonist. This response was dependent on H1 receptors, since it was reduced in the presence of H1-receptor antagonist. It is suggested that interaction between histamine and adenosine modulating induction of second messengers in HBEC may influence endothelium-dependent responses of brain microvascular compartments.